The significance of finerenone as a novel therapeutic option in diabetic kidney disease: a scoping review with emphasis on cardiorenal outcomes of the finerenone phase 3 trials.

This scoping review prepared by endocrinology and nephrology experts aimed to address the significance of finerenone, as a novel therapeutic option, in diabetic kidney disease (DKD), based on the biological prospect of cardiorenal benefit due to non-steroidal mineralocorticoid receptor antagonist (MRA) properties, and the recent evidence from the finerenone phase 3 program clinical trials. The importance of finerenone in slowing DKD progression was critically reviewed in relation to the role of MR overactivation in the pathogenesis of cardiorenal disease and unmet needs in the current practice patterns. The efficacy and safety outcomes of finerenone phase III study program including FIDELIO-DKD, FIGARO-DKD and FIDELITY were presented. Specifically, perspectives on inclusion of patients with preserved estimated glomerular filtration rate (eGFR) or high albuminuria, concomitant use of sodium-glucose co-transporter-2 inhibitor (SGLT2i) or glucagon-like peptide 1 receptor agonist (GLP-1 RA), baseline glycated hemoglobin (HbA1c) level and insulin treatment, clinically meaningful heart failure outcomes and treatment-induced hyperkalemia were addressed. Finerenone has emerged as a new therapeutic agent that slows DKD progression, reduces albuminuria and risk of cardiovascular complications, regardless of the baseline HbA1c levels and concomitant treatments (SGLT2i, GLP-1 RA, or insulin) and with a favorable benefit-risk profile. The evolving data on the benefit of SGLT2is and non-steroidal MRAs in slowing or reducing cardiorenal risk seem to provide the opportunity to use these pillars of therapy in the management of DKD, after a long-period of treatment scarcity in this field. Along with recognition of the albuminuria as a powerful marker to detect those patients at high risk of cardiorenal disease, these important developments would likely to impact standard-of-care options in the setting of DKD.

Impact of Sodium-Glucose Cotransporter-2 Inhibitors in the Management of Chronic Kidney Disease: A Middle East and Africa Perspective.

Chronic kidney disease (CKD) is a major public health concern in the Middle East and Africa (MEA) region and a leading cause of death in patients with type 2 diabetes mellitus (T2DM) and hypertension. Early initiation of sodium-glucose cotransporter - 2 inhibitors (SGLT-2i) and proper sequencing with renin-angiotensin-aldosterone system inhibitors (RAASi) in these patients may result in better clinical outcomes due to their cardioprotective properties and complementary mechanisms of action. In this review, we present guideline-based consensus recommendations by experts from the MEA region, as practical algorithms for screening, early detection, nephrology referral, and treatment pathways for CKD management in patients with hypertension and diabetes mellitus. This study will help physicians take timely and appropriate actions to provide better care to patients with CKD or those at high risk of CKD.

Clinical Characteristics of Rapid Progression in Asia-Pacific Patients With ADPKD.

Introduction: This study aimed to determine the utility of different methods to predict rapid progressors (RPs) and their clinical characteristics in Asia-Pacific patients with autosomal dominant polycystic kidney disease (ADPKD). Methods: This was a multinational retrospective observational cohort study of patients with ADPKD in the Asia-Pacific region. Five hospitals from Australia, China, South Korea, Taiwan, and Turkey participated in this study. RP was defined by European Renal Association-European Dialysis and Transplantation Association (ERA-EDTA) guidelines and compared to slow progressors (SPs). Results: Among 768 patients, 426 patients were RPs. Three hundred six patients met only 1 criterion and 120 patients satisfied multiple criteria for RP. Historical estimated glomerular filtration rate (eGFR) decline fulfilled the criteria for RP in 210 patients. Five patients met the criteria for a historical increase in height-adjusted total kidney volume (TKV). The 210 patients satisfied the criteria for based on kidney volume. During the follow-up period, cyst infections, cyst hemorrhage, and proteinuria occurred more frequently in RP; and 13.9% and 2.1% of RPs and SPs, respectively, progressed to end-stage kidney disease (ESKD). RP criteria based on historical eGFR decline had the strongest correlation with eGFR change over a 2-year follow-up. Conclusion: Various assessment strategies should be used for identifying RPs among Asian-Pacific patients with ADPKD in real-world clinical practice during the follow-up period, cyst infections, cyst hemorrhage, and proteinuria occurred more frequently; and more patients progressed to ESKD in RPs compared with SPs.

Chronic Kidney Disease Management in the Middle East and Africa: Concerns, Challenges, and Novel Approaches.

The burden of chronic kidney disease (CKD) and other comorbidities, such as hypertension and diabetes, which increase the risk of developing CKD, is on the rise in the Middle East and Africa. The Middle East and Africa CKD (MEA-CKD) steering committee, comprising eminent healthcare specialists from the Middle East and Africa, was formed to identify and propose steps to address the gaps in the management of CKD in these regions. The current article lists the MEA-CKD steering committee meeting outcomes and evaluates the available evidence supporting the role of novel therapeutic options for patients with CKD. The need of the hour is to address the gaps in awareness and screening, early diagnosis, along with referral and management of patients at risk. Measures to bring about appropriate changes in healthcare policies to ensure access to all benefit-proven protective therapies, including novel ones, at community levels are also vital for reducing the overall burden of CKD on the healthcare system as well as governing bodies, especially in developing countries of the Middle East and Africa.

Correlation of Luminex-Based Single Antigen Based Results With Complement-Dependent Cytotoxicity Crossmatch and Flow Cytometry Crossmatch Results: A Single-Center Experience From Istanbul.

BACKGROUND: This study aimed to retrospectively investigate the correlation of mean Class I donor-specific antibody (DSA) intensity values detected in Luminex-based techniques with the results of complement-dependent cytotoxicity crossmatch (CDC-XM) and flow cytometry crossmatch (FC-XM) results. METHODS: A total of 335 patients with kidney failure and their living donors whose CDC-XM, FC-XM, and single antigen based (SAB) tests were studied between 2018 and 2020 for transplant preparation from living donor candidates were included in the study. Patients were divided into 4 groups according to their mean fluorescence intensity (MFI) values of SAB assay. RESULTS: Anti-HLA antibodies (class I and/or class II) were detected using SAB in 91.6% patients included in the study (MFI >1000). Class I DSA was positive in 34.8% of patients with anti-HLA antibodies. When CDC-XM and FC-XM results were evaluated in the 4 groups separated according to MFI values, 3 patients with DSA MFI <1000 had negative CDC-XM and T-B-FC-XM results. Of 32 patients with DSA-MFI between 1000 and 3000, 93.75% (n = 30) had T-B-FC-XM or CDC-XM-negative results, and 6.25% (n = 2) had B-FC-XM-positive results. The CDC-XM, T, and B-FC-XM were negative in all 17 patients with DSA-MFI between 3000 and 5000. Our results showed that MFI >5834 DSA values were significantly correlated with positive T-FC-XM (P < .001), and MFI >6016 values were significantly correlated with positive CDC-XM (P = .002). In addition, MFI values >5000 were associated with both CDC-XM and FC-XM in our study. CONCLUSIONS: The MFI values >5000 correlated with both CDC-XM and FC-XM.

Effect of the arterial needle bevel position on puncture pain and postremoval bleeding time in hemodialysis patients: A self-controlled, single-blind study.

AIM: This study aimed to investigate the effect of the bevel orientation (facing upwards or downwards towards the skin) of the needle inserted into the arterial limb of the arteriovenous fistula (AVF) on puncture pain and postremoval bleeding time. METHODS: This study, using a single-blind crossover design, was conducted on 35 maintenance hemodialysis patients who had been dialyzed for at least 6 months and in whom blood access was via an AVF. AVF cannulation was performed with the needle bevel pointing upward in the first six sessions and the needle bevel pointing downwards (towards the skin) in the subsequent six sessions. Needles were always inserted in the direction of blood flow. At each dialysis session, cannulation pain was measured using a visual analog scale (VAS), and the bleeding time at the end of dialysis after needle removal was recorded. FINDINGS: The VAS score and postremoval bleeding time were lower when the needle bevel pointed downwards towards the skin during insertion (P < 0.05). DISCUSSION: Insertion of the needle with the bevel pointed downward decreased puncture pain during cannulation and bleeding time postdialysis on needle removal.

Subclinic arterial and left ventricular systolic impairment in autosomal dominant polycystic kidney disease with preserved renal functions.

Subclinical atherosclerosis and cardiovascular events are common even in young normotensive patients with autosomal dominant polycystic kidney disease (ADPKD). Our aim was to examine the relationship between serum fibroblast growth factor-23 (FGF-23) levels, left ventricular global longitudinal strain (LV-GLS), arterial stiffness (AS), and carotid intima-media thickness (CIMT) in patients with ADPKD with preserved kidney function. The relationship between albuminuria, AS, LV-GLS, CIMT, 24-hour ambulatory blood pressure measurement, and FGF-23 was examined in 52 normotensive and hypertensive patients with ADPKD and a matched control group of 35 subjects. AS was assesed with brachial-ankle pulse wave velocity, LV-GLS was measured with speckle-tracking echocardiography. FGF-23 was measured with enzyme-linked immunosorbent assay. The microalbumin/creatinine ratio was significantly higher in the ADPKD group than in the control group (p?

The Relationship between Serum Ferritin Levels and 5-Year All-Cause Mortality in Hemodialysis Patients.

INTRODUCTION: The effect of high serum ferritin levels on long-term mortality in hemodialysis patients is unknown. The relationship between serum ferritin levels and 5-year all-cause mortality in hemodialysis patients was investigated in this study. METHODS: A total of 173 prevalent hemodialysis patients were included in this study. The patients were followed for up to 5 years and divided into 3 groups according to time-averaged serum ferritin levels (group 1: serum ferritin <800 ng/mL, group 2: serum ferritin 800-1,500 ng/mL, and group 3: serum ferritin >1,500 ng/mL). Along with the serum ferritin levels, other clinical and laboratory variables that may affect mortality were also included in the Cox proportional-hazards regression analysis. RESULTS: Eighty-one (47%) patients died during the 5-year follow-up period. The median follow-up time was 38 (17.5-60) months. The 5-year survival rates of groups 1, 2, and 3 were 44, 64, and 27%, respectively. In group 3, the survival was lower than in groups 1 and 2 (log-rank test, p = 0.002). In group 1, the mortality was significantly lower than in group 3 (HR [95% CI]: 0.16 [0.05-0.49]; p = 0.001). In group 2, the mortality was also lower than in group 3 (HR [95% CI]: 0.32 [0.12-0.88]; p = 0.026). No significant difference in mortality between groups 1 and 2 was found (HR [95% CI]: 0.49 [0.23-1.04]; p = 0.063). CONCLUSION: Time-averaged serum ferritin levels >1,500 ng/mL in hemodialysis patients are associated with an increased 5-year all-cause mortality risk.

The effect of chewing gum on dry mouth, interdialytic weight gain, and intradialytic symptoms: A prospective, randomized controlled trial.

INTRODUCTION: The major salivary glands can be stimulated by chewing gum to increase saliva flow and decrease xerostomia. The aim of this study was to investigate the effect of chewing gum on dry mouth, interdialytic weight gain, and intradialytic symptoms in hemodialysis (HD) patients. METHODS: This prospective randomized controlled single-blind study was conducted with patients who had been treated for at least 6 months with sessions 3 days a week for 4 hours at two HD units. Patients were randomly allocated to chewing gum group or the control group. In the chewing gum group, gum was chewed for 10 minutes six times a day, and when the patients felt mouth dryness or were thirsty. In the nonchewing gum group, gum was not chewed. The patients were followed-up for 3 months. A total of three saliva samples were taken before starting treatment at the first, 12th, and 36th HD session. Data were collected with the "Visual Analogue Scale (VAS)," "Hemodialysis Patients Fluid Control Scale," "Dialysis Symptom Index," and "Hospital Anxiety and Depression Scale" at baseline, week 4, week 8, and week 12. FINDINGS: The study was completed with a total of 44 patients consisting of 22 patients in the each group. The second and third month VAS values (xerostomia) of the patients in the chewing gum groups were statistically significantly lower than those in the control group (P = 0.014, P < 0.001, respectively). The third month salivary flow rate in the chewing gum group was higher than the values in the control group patients (P < 0.001). DISCUSSION: It is anticipated that this study will raise nurses' awareness of dry mouth and encourage future studies on interventions to increase the salivary flow rate to prevent or treat dry mouth.

RAPID-ADPKD (Retrospective epidemiological study of Asia-Pacific patients with rapId Disease progression of Autosomal Dominant Polycystic Kidney Disease): study protocol for a multinational, retrospective cohort study.

INTRODUCTION: Patients with autosomal dominant polycystic kidney disease (ADPKD) reach end-stage renal disease in their fifth decade on average. For effective treatment and early intervention, identifying subgroups with rapid disease progression is important in ADPKD. However, there are no epidemiological data on the clinical manifestations and disease progression of patients with ADPKD from the Asia-Pacific region. METHODS AND ANALYSIS: The RAPID-ADPKD (Retrospective epidemiological study of Asia-Pacific patients with rapId Disease progression of Autosomal Dominant Polycystic Kidney Disease) study is a multinational, retrospective, observational cohort study of patients with ADPKD in the Asia-Pacific region (Australia, China, Hong Kong, South Korea, Taipei and Turkey). This study was designed to identify the clinical characteristics of patients with ADPKD with rapid disease progression. Adult patients with ADPKD diagnosed according to the unified ultrasound criteria and with an estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m2 at baseline will be included. The cohort will include patients with ≥2 records of eGFR and at least 24 months of follow-up data. Demographic information, clinical characteristics, comorbidities, medications, eGFR, radiological findings that allow calculation of height-adjusted total kidney volume, ADPKD-related complications and the Predicting Renal Outcomes in autosomal dominant Polycystic Kidney Disease (PRO-PKD) score will be collected. Rapid progression will be defined based on the European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) guideline. All other patients without any of these criteria will be classified to be of slow progression. Clinical characteristics will be compared between patients with rapid progression and those with slow progression. The incidence of complications and the effects of race and water intake on renal progression will also be analysed. The planned sample size of the cohort is 1000 patients, and data from 600 patients have been collected as of 30 May 2019. ETHICS AND DISSEMINATION: This study was approved or is in the process of approval by the institutional review boards at each participating centre. The results will be presented in conferences and published in a journal, presenting data on the clinical characteristics, risk factors for disease progression and patterns of complications of ADPKD in Asian populations.

Dietary Patterns and Mortality in a Multinational Cohort of Adults Receiving Hemodialysis.

RATIONALE & OBJECTIVE: Clinical practice guidelines for dietary intake in hemodialysis focus on individual nutrients. Little is known about associations of dietary patterns with survival. We evaluated the associations of dietary patterns with cardiovascular and all-cause mortality among adults treated by hemodialysis. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 8,110 of 9,757 consecutive adults on hemodialysis (January 2014 to June 2017) treated in a multinational private dialysis network and with analyzable dietary data. EXPOSURES: Data-driven dietary patterns based on the GA2LEN food frequency questionnaire. Participants received a score for each identified pattern, with higher scores indicating closer resemblance of their diet to the identified pattern. Quartiles of standardized pattern scores were used as primary exposures. OUTCOMES: Cardiovascular and all-cause mortality. ANALYTICAL APPROACH: Principal components analysis with varimax rotation to identify common dietary patterns. Adjusted proportional hazards regression analyses with country as a random effect to estimate the associations between dietary pattern scores and mortality. Associations were expressed as adjusted HRs with 95% CIs, using the lowest quartile score as reference. RESULTS: During a median follow-up of 2.7 years (18,666 person-years), there were 2,087 deaths (958 cardiovascular). 2 dietary patterns, "fruit and vegetable" and "Western," were identified. For the fruit and vegetable dietary pattern score, adjusted HRs, in ascending quartiles, were 0.94 (95% CI, 0.76-1.15), 0.83 (95% CI, 0.66-1.06), and 0.91 (95% CI, 0.69-1.21) for cardiovascular mortality and 0.95 (95% CI, 0.83-1.09), 0.84 (95% CI, 0.71-0.99), and 0.87 (95% CI, 0.72-1.05) for all-cause mortality. For the Western dietary pattern score, the corresponding estimates were 1.10 (95% CI, 0.90-1.35), 1.11 (95% CI, 0.87-1.41), and 1.09 (95% CI, 0.80-1.49) for cardiovascular mortality and 1.01 (95% CI, 0.88-1.16), 1.00 (95% CI, 0.85-1.18), and 1.14 (95% CI, 0.93-1.41) for all-cause mortality. LIMITATIONS: Self-reported food frequency questionnaire, data-driven approach. CONCLUSIONS: These findings did not confirm an association between mortality among patients receiving long-term hemodialysis and the extent to which dietary patterns were either high in fruit and vegetables or consistent with a Western diet.

Fruit and Vegetable Intake and Mortality in Adults undergoing Maintenance Hemodialysis.

BACKGROUND AND OBJECTIVES: Higher fruit and vegetable intake is associated with lower cardiovascular and all-cause mortality in the general population. It is unclear whether this association occurs in patients on hemodialysis, in whom high fruit and vegetable intake is generally discouraged because of a potential risk of hyperkalemia. We aimed to evaluate the association between fruit and vegetable intake and mortality in hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Fruit and vegetable intake was ascertained by the Global Allergy and Asthma European Network food frequency questionnaire within the Dietary Intake, Death and Hospitalization in Adults with ESKD Treated with Hemodialysis study, a multinational cohort study of 9757 adults on hemodialysis, of whom 8078 (83%) had analyzable dietary data. Adjusted Cox regression analyses clustered by country were conducted to evaluate the association between tertiles of fruit and vegetable intake with all-cause, cardiovascular, and noncardiovascular mortality. Estimates were calculated as hazard ratios with 95% confidence intervals (95% CIs). RESULTS: During a median follow up of 2.7 years (18,586 person-years), there were 2082 deaths (954 cardiovascular). The median (interquartile range) number of servings of fruit and vegetables was 8 (4-14) per week; only 4% of the study population consumed at least four servings per day as recommended in the general population. Compared with the lowest tertile of servings per week (0-5.5, median 2), the adjusted hazard ratios for the middle (5.6-10, median 8) and highest (>10, median 17) tertiles were 0.90 (95% CI, 0.81 to 1.00) and 0.80 (95% CI, 0.71 to 0.91) for all-cause mortality, 0.88 (95% CI, 0.76 to 1.02) and 0.77 (95% CI, 0.66 to 0.91) for noncardiovascular mortality and 0.95 (95% CI, 0.81 to 1.11) and 0.84 (95% CI, 0.70 to 1.00) for cardiovascular mortality, respectively. CONCLUSIONS: Fruit and vegetable intake in the hemodialysis population is low and a higher consumption is associated with lower all-cause and noncardiovascular death.

Hand-Assisted Nephrectomy Predisposes Incisional Herniation in Obese Living Donors.

BACKGROUND: Living kidney donation from donors with a body mass index (BMI) over 30 can bring risks for the donor and the recipients. In this retrospective study, we evaluated the effect of a donor's obesity on a donor's long-term surveillance and the recipient outcomes. METHOD: We performed hand-assisted retroperitoneoscopic donor nephrectomy in 565 living kidney transplantations between February 2009 and December 2015. One hundred fifty-two donors (26.9%) had a BMI > 30 and were described as the obese group. Four hundred thirteen donors (73.1%) were described as the nonobese group and had a BMI < 30. Incision to kidney removal time, mean follow-up period, postoperative complications, weight gained after surgery, and serum creatinine level (postop day 1-end of follow-up) were recorded for the donors. Serum creatinine level (postop day 5-end of follow-up) and immediate function of transplanted kidney were recorded for the recipients. RESULTS: The obese donors were older, and the female sex was dominant. Mean incision to kidney removal period was longer in the obese patients (P = .012). The mean follow-up period was 49.97 ± 28.40 months for the donors. There was no significant difference in donor kidney function between the groups. The incidence of herniation was significantly higher in the obese group (P = .021). There was no significant difference between the recipient early and late serum creatinine levels and slow and delayed graft functions after the transplantation. CONCLUSION: Postoperative kidney functions concerning the outcomes of the obese and nonobese living donors were similar in our series. Donor BMI had no influence on early and late kidney functions of the recipients. There was no difference in postoperative complications, except incisional hernia, that was statistically more significant in the obese donors.

Dysmetabolic markers predict outcomes in autosomal dominant polycystic kidney disease.

BACKGROUND: Overweight and obesity were recently associated with a poor prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD). Whether the metabolic consequences of obesity as defined by the metabolic syndrome (MS) are also linked with disease progression remains untested. METHODS: Eligible ADPKD patients with different stages of CKD (n = 105) and 105 non-diabetic controls matched for CKD stage were enrolled in the study. Groups were evaluated at baseline for presence of MS, blood markers of metabolism, homeostasis model assessment of insulin resistance (HOMA-IR) score, and biochemical markers of inflammation (hs-CRP, IL-1ß, IL-6, TNF-α and PON-1). MS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Patients were followed for 12 months and progression defined as a decrease in baseline eGFR > 10%. RESULTS: MS and hypertension were more prevalent amongst ADPKD patients than in the control group. Meanwhile, markers of inflammation such as hs-CRP (3.63 [3.45-5.17] vs. 4.2 [3.45-8.99] mg/dL; p = 0.014), IL-6 (21.65 [14.1-27.49] vs. 24.9 [16.23-39.4] pg/mL; p = 0.004) and IL-1ß (21.33 [15.8-26.4] vs. 26.78 [18.22-35] pg/mL; p < 0.001) levels were all more elevated in ADPKD patients than in non-diabetic CKD subjects. In multivariate analysis having a truncating PKD1 mutation predicted (OR 1.25 [1.09-1.43]; p = 0.002) fulfilling the MS criteria. Finally, ADPKD patients fulfilling MS criteria had a significantly more rapid progression during 12 months of follow-up than did those that did not (OR 3.28 [1.09-9.87]; p = 0.035). CONCLUSIONS: Our data supports the notion that dysmetabolisms part of the ADPKD phenotype and associated with a poor outcome, especially in patients with a truncating PKD1 mutation.

Fabry Disease Prevalence in Renal Replacement Therapy in Turkey.

BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from lack of alpha-galactosidase A (AGALA) activity in lysosomes. OBJECTIVE: In this multicenter study, we aimed to evaluate the prevalence of FD in renal transplant (Tx) recipients in Turkey. We also screened dialysis patients as a control group. METHODS: All Tx and dialysis patients were screened regardless of the presence of a primary disease. We measured the AGALA activity in all male patients as initial analysis. Mutation analysis was performed in male patients with decreased AGALA activity and in female patients as the initial diagnostic assay. RESULTS: We screened 5,657 patients. A total of 17 mutations were identified. No significant difference was observed between the groups regarding the prevalence of patients with mutation. We found FD even in patients with presumed primary kidney diseases. Seventy-one relatives were analyzed and mutation was detected in 43 of them. We detected a patient with a new, unknown mutation (p.Cys223) in the GLA gene. CONCLUSIONS: There are important implications of the screening. First, detection of the undiagnosed patients leads to starting appropriate therapies for these patients. Second, the transmission of the disease to future generations may be prevented by prenatal screening after appropriate genetic counseling. In conclusion, we suggest screening of kidney Tx candidates for FD, regardless of etiologies of chronic kidney disease.